[Probability of the combination use of cisplatin and carboplatin].
To investigate whether each of cisplatin (CDDP) and carboplatin (CBDCA) was AUC (Area Under the Curve)-dependent or time-dependent drug, Human Tumor Clonogenic Assays (HTCA) were performed in various exposure times of CDDP or CBDCA using PC-9 cells. From the result of this study, it was shown that CDDP and CBDCA were AUC dependent drugs. Furthermore, to evaluate the combination effect of CDDP and CBDCA, we carried out HTCA using PC-9 and PC-14 (human lung adenocarcinoma cell lines) cells, and evaluated the combination effect by the median effect analysis of Chou, T.C. and Talalay, P. The combination effects were above the additive effects at the AUC ratios of free Pt in the exposure medium of 3.2, 6.5, 13.1 (CBDCA/CDDP). Especially in the combination of 3 hours exposure of CBDCA followed by 1 hour exposure of CDDP, the Combination Index by median effect analysis was from 0.74 to 0.86 at the AUC ratio of 13.1. But the combination effect was antagonistic at that of 19.5. CDDP and CBDCA, which are AUC dependent drugs, have shown different side effects in previous clinical practice. And the combination effect of both drugs is more than additive effect at the AUC ratios of free Pt of 3.2, 6.5, 13.1 (CBDCA/CDDP). It is considered that the combination chemotherapy of CDDP and CBDCA for patients of lung adenocarcinoma may be useful.
Kobayashi
K
K
Department of Clinical Pathology, Nippon Medical School.
Hino
M
M
Hayashihara
K
K
Niitani
H
H
D000230:Adenocarcinoma / Q000473:pathology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D016190:Carboplatin / Q000008:administration & dosage / Q000494:pharmacology*; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay
D016190:Carboplatin; D002945:Cisplatin